Dyssynchronous Ca(2+) sparks in myocytes from infarcted hearts.

Abstract:

:The kinetics of contractions and Ca(2+) transients are slowed in myocytes from failing hearts. The mechanisms accounting for these abnormalities remain unclear. Myocardial infarction (MI) was produced by ligation of the circumflex artery in rabbits. We used confocal microscopy to record spatially resolved Ca(2+) transients during field stimulation in left ventricular (LV) myocytes from control and infarcted hearts (3 weeks). Compared with controls, Ca(2+) transients in myocytes adjacent to the infarct had lower peak amplitudes and prolonged time courses. Control myocytes showed relatively uniform changes in [Ca(2+)] throughout the cell after electrical stimulation. In contrast, in MI myocytes [Ca(2+)] increased inhomogeneously and localized increases in [Ca(2+)] occurred throughout the rising and falling phases of the Ca(2+) transient. Ca(2+) content of the sarcoplasmic reticulum did not differ between MI and control myocytes. Peak L-type Ca(2+) current density was reduced in MI myocytes. The macroscopic gain function was not different in control and MI myocytes when calculated as the amplitude of the Ca(2+) transient/peak I:(Ca). However, when calculated as the peak rate of rise of the Ca(2+) transient/peak I:(Ca), the gain function was modestly decreased in the MI myocytes. Application of isoproterenol (100 nmol/L) improved the synchronization of Ca(2+) release in MI myocytes at both 0.5 and 1 Hz. The poorly coordinated production of Ca(2+) sparks in myocytes from infarcted rabbit hearts likely contributes to the diminished and slowed macroscopic Ca(2+) transient. These abnormalities can be largely overcome when phosphorylation of Ca(2+) cycling proteins is enhanced by ss-adrenergic stimulation.

journal_name

Circ Res

journal_title

Circulation research

authors

Litwin SE,Zhang D,Bridge JH

doi

10.1161/01.res.87.11.1040

subject

Has Abstract

pub_date

2000-11-24 00:00:00

pages

1040-7

issue

11

eissn

0009-7330

issn

1524-4571

journal_volume

87

pub_type

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